To: Mike McFarland who wrote (25 ) 2/10/2009 6:26:02 AM From: Mike McFarland Read Replies (1) | Respond to of 50 One of the benefits of shift worker insomnia-- you catch UWTV lectures at 3am (PDT). This was short lecture on the scientific rationale for >decreasing< norepinephrine in Alzheimers. Has nothing to do with ORXE, but if we had a DR (drug repurposing) thread I'd put this there. I found the poster for the study--the lecturer jokingly called this 'reduce agitation for a dime a day'--just a nice example of repurposing.download.journals.elsevierhealth.com PRAZOSIN FOR TREATMENT OF DISRUPTIVE AGITATION IN ALZHEIMER’S DISEASE Lucy Y. Wang1,2, Eric C. Petrie1,2, Kirsten Rohde2, Kim L. Hart2, David J. Hoff2, Jane B. Shofer2, Murray A. Raskind1,2, Elaine R. Peskind1,2, 1University of Washington, Seattle, WA, USA; 2VA Puget Sound Health Care System, Seattle, WA, USA. Contact e-mail: wanglucy@u.washington.edu Background: Disruptive agitation in Alzheimer’s disease (AD) is a major cause of patient distress, home and facility caregiver burden, and institutionalization. Previous research suggests that enhanced behavioral responsiveness to CNS norepinephrine release contributes to the pathophysiology of agitation in AD. Prazosin, a generic drug used to treat hypertension, antagonizes norepinephrine effects at CNS postsynaptic alpha-1 adrenoreceptors. This study is a pilot placebo-controlled trial of prazosin for disruptive agitation in AD. Methods: Twenty-one nursing home and community dwelling participants with disruptive agitation and probable or possible AD (mean age 80.3 11.3) were randomized to placebo (n11) or prazosin (n10) in a parallel group double-blind study. Medication was initiated at 1mg/day and increased up to 6mg/day in divided doses using a flexible dosing algorithm. Participants continued their maximum achieved dose for eight weeks. Outcome measures were the Brief Psychiatric Rating Scale (BPRS), Neuropsychiatric Inventory (NPI), and Clinical Global Impression of Change (CGIC). Results: The overall completion rate was 57% and did not differ between prazosin and placebo groups. Participants taking prazosin (mean dose 5.7 0.95mg/day) had greater improvements than those taking placebo (mean dose 5.6 1.2mg/day) on the CGIC (mean 2.7 1.1 versus 4.5 1.6, p0.008), BPRS (mean change -10.0 9.0 versus -3.5 4.1, p0.035), and NPI (mean change -19.1 22.4 versus -3.7 15.3, p0.038). Prazosin was well tolerated. Blood pressure changes did not differ between prazosin and placebo groups. Conclusions: Prazosin may be effective for the treatment of disruptive agitation in AD. These findings need to be confirmed in larger studies.